title: Menin promotes hepatocellular carcinogenesis and epigenetically up-regulates Yap1 transcription.
abstract: Menin is a scaffold protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene in humans, and it interacts with a variety of transcriptional proteins to control active or repressive cellular processes. Here, we show that heterozygous ablation of Men1 in female mice reduces chemical carcinogen-induced liver carcinogenesis and represses the activation of the inflammation pathway. Using ChIP-on-chip screens and ChIP assays, we find that menin occupancy frequently coincides with H3K4me3 at the promoter of many liver cancer-related genes, such as Yes-associated protein (Yap1). Increased menin and Yap1 expression in human hepatocellular carcinoma specimens was associated with poor prognosis. Our findings reveal that menin plays an important epigenetic role in promoting liver tumorigenesis, and support the notion that H3K4me3, which is regulated by the menin-mixed-lineage leukemia complex, is a potential therapeutic target in hepatocellular carcinoma.
authors.affiliation: Department of Basic Medical Sciences of Medical College, State Key Laboratory of Cellular Stress Biology, and Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen University, Xiamen 361102, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Shan-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.forename: Shu-Bin
authors.initials: SB
authors.lastname: Gao
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Ding
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Yin
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.forename: Zi-Jie
authors.initials: ZJ
authors.lastname: Feng
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Jin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D063646:Carcinogenesis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004052:Diethylnitrosamine; D044127:Epigenesis, Genetic; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics*; D034622:RNA Interference; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C484898:Men1 protein, mouse; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D004052:Diethylnitrosamine; D002251:Carbon Tetrachloride
keywords: H3K4 methylation; interleukin 6